Biodegradable material components

ABSTRACT

A biodegradable material for use in making items usable in surgery and related fields of medicine. The material comprising a bioabsorbable thermoplastic polymer component and a bioactive filler material. In components made of the material particles of the filler material occur embedded within the surface of the components.

[0001] This invention concerns components made of biodegradablematerials, a method of making such materials, such materials, and amethod of making such components.

[0002] Orthopaedic surgery, craniofacial surgery and related fields ofmedicine require the use of materials which are suitable as implants andprostheses, for example to fill voids created by surgical removal ofbone or tissue, or in the formation of screws, pins or plates to holdtogether bone surfaces or attach ligaments or tendons whilst naturalhealing takes place. Such materials must, particularly when they areused as load bearing implants, possess good mechanical strength and asufficiently high Young's modulus to provide secure fixation. Commonlyused prosthetic materials include metals such as cobalt—chromium alloys,titanium and stainless steel. Many studies however, have shown that thehigh rigidity of these materials can prevent complete healing since muchof the load which is normally carried by the bone is transferred acrossthe defect site by the implant i.e. producing a stress shielding effect.In addition, metallic implants can have a number of other disadvantagesincluding long term metal ion release and often the need for furthersurgery to remove the implant.

[0003] Bioabsorbable polymers are a class of materials that are nowbeing used in a wide range of medical applications. These include softtissue support such as sutures and wound care patches and hard tissuerepair and fixation such as plates, screws and pins. The rate of healingof bone and the establishment of viable haversian systems is about sixweeks in man and hence materials for fracture support should maintainadequate strength and modulus throughout this time frame.

[0004] The invention provides a component made of a biodegradablematerial which material comprises a bioabsorbable polymer component anda bioactive filler material, wherein particles of the filler occurembedded within the surface of the component.

[0005] The component may comprise any of a screw, pin, plate, suture,wound care patch, spinal spacer, osteotomy wedge, cement restrictor,non-woven mesh or other item usable in surgery and related fields ofmedicine.

[0006] According to the present invention there is also provided amethod of making a biodegradable material, the method comprising mixingtogether a bioabsorbable polymer component and a bioactive fillermaterial.

[0007] The polymer component and filler are preferably mixed together inthe form of granules each having similar particle size ranges. Theparticle size may be between 0.5 mm and 5 mm.

[0008] The polymer component and filler may be mixed together in theform of dry particulate materials.

[0009] Alternatively the polymer component may be coated with thefiller.

[0010] The polymer component may be wetted with a solvent prior to orduring mixing and the solvent may comprise chloroform. The polymercomponent may be sprayed onto the filler.

[0011] The material is preferably subsequently dried to remove thesolvent.

[0012] The particle size of the polymer component may be reduced priorto mixing with the filler. The polymer component may be milled and maybe cryogenically milled.

[0013] The particle size of the filler may be increased prior to mixingwith the polymer component, and the filler material may be caused toagglomerate or granulate.

[0014] The invention further provides a biodegradable material, thematerial being formed by a method according to any of the precedingeight paragraphs.

[0015] The mixture is preferably substantially homogeneous.

[0016] The polymer component is preferably synthetic, and may comprise apolyester.

[0017] The polymer component preferably comprises one or more polymersor co-polymers of lactic acid (L and/or D), glycolic acid,hydroxybutyric acid, hydroxyvaleric acid, poly dioxanone, polycaprolactone, poly ethylene oxide or poly butylene terephthalate.

[0018] The filler may comprise alone or in combination, a calciumphosphate, calcium sulphate or carbonate bioceramic filler, or abioactive glass. The filler preferably comprises hydroxyapatite and/orbeta tri-calcium phosphate.

[0019] The filler preferably has a particle size of substantially lessthan 100 microns. The filler preferably constitutes between 1% and 50%of the mixture by weight, and desirably between 15% and 35%.

[0020] The filler may additionally comprise, alone or in combination, asacrificial porosifier. The sacrificial porosifier may comprise a watersoluble, heat stable inorganic salt. The inorganic salt may comprisesodium chloride. The sodium chloride may be in the form of a finelydivided powder. The sodium chloride may constitute between 1% and 50% byweight of the material.

[0021] The material preferably substantially comprises no mechanicallyfree filler particles with a diameter less than 100 microns.

[0022] The invention also provides a method of making a component, themethod comprising moulding a material according to any of said precedingeight paragraphs.

[0023] The moulding may be in the form of injection moulding,compression moulding, extrusion, extrusion followed by drawing, meltspinning or other melt forming technique.

[0024] The material is preferably fed to a moulding machine, with atleast a substantial proportion of the material in the form of granuleswith a diameter of between 0.5 and 5 mm.

[0025] The material may be dried prior to moulding.

[0026] The component may be annealed subsequent to moulding.

[0027] Embodiments of the present invention will now be described by wayof example only, and with reference to the single accompanying drawingwhich is a SEM micrograph of the surface of a component according to theinvention.

EXAMPLE 1

[0028] A poly L-lactide (PLLA) of molecular weight 200,000 Daltons andmean granule size of 4 mm was added to a pan granulator together with apoly crystalline micro porous beta tri-calcium phosphate (TCP) powder ofmean particle size 10 microns and having no particles greater than 50microns diameter. The crystallite size of the beta TCP was approximately1 micron. The ratio of polymer to calcium phosphate was 5:1 parts byweight. The pan granulator was set in motion and a spray of chloroformwas directed at the tumbling mass of granules. The PLLA immediatelybecame wetted by the chloroform and the TCP powder adhered to theresulting “sticky” polymer surface. When all of the TCP appeared to havecoated the PLLA granules the granulation process was stopped. Theresultant TCP coated PLLA was dried in an oven at 100° C. for 4 hours toremove all traces of chloroform and then fed into an injection mouldingmachine where bony site implantation devices were moulded. A microscopicexamination of the surface of the moulded components revealed calciumphosphate particles embedded within and exposed at the said surface.

EXAMPLE 2

[0029] A poly L-lactide of molecular weight 200,000 Daltons and meangranule size of 4 mm was cryogenically milled to give polymer flakes ofsize range approximately ½ mm to 1½ mm with an absence of finermaterial.

[0030] A beta tri-calcium phosphate powder of mean particle size 10microns and having no particles greater than 50 microns diameter wasdispersed in water. The resulting slurry was de-watered on a Buchnerfilter and the resulting filter cake was dried. The dry cake was lightlycrushed and sieved to give loose agglomerates in the size range ofapproximately ½ mm to 1½ mm. These agglomerates were now lightlysintered followed by dry mixing with PLLA flakes in the proportionsPLLA:TCP, 3:1 by weight. The resulting mix could now be fed through thehopper into the injection moulder without problems of demixing orbridging. Inside the moulding machine the high shear conditions withinthe viscous polymer melt caused break-up of the lightly sintered TCPagglomerates. Moulded composite implantation devices were produced whichhad a uniform dispersion of TCP particles of substantially less than 100micron diameter within both the bulk and the surface of the polymermatrix.

EXAMPLE 3

[0031] A hydroxyapatite (HA) powder having a maximum particle size ofabout 50 microns was put into a pan granulator. While tumbling, the HApowder was sprayed with a solution of poly L-lactide of molecular weight150,000 Daltons in chloroform at a concentration of 2 gms PLLA in 100 mlof chloroform. Spraying was stopped when the granules reached a maximumsize of approximately 3 mm. The product was dried at 100° C. for 2 hoursto remove residual solvent and any remaining powder less than 500 micronparticle size was sieved out of the mix The granulated HA was now dryblended with PLLA granules of molecular weight 220,000 Daltons andparticle size 2 mm to 3 mm in a weight ratio of PLLA:HA, 2:1. Themixture was fed to an injection moulding machine and moulded componentswere produced which had HA particles embedded within their surface andthroughout their bulk.

EXAMPLE 4

[0032] A poly L-lactide of molecular weight 200,000 Daltons and meangranule size of 4 mm was cryogenically milled to give polymer flakes ofsize range approximately ½ mm to 1½ mm with an absence of finermaterial.

[0033] A lightly sintered polycrystalline hydroxyapatite powder having aparticle size of about 100-250 microns was dry blended with the PLLAflakes in the proportions PLLA:HA 3:1 by weight and the mixture washeated to 145° C. for ½ hour. This temperature is not so high as to meltthe polymer and start the degradation process but is sufficient to givesome “stickiness” and hence cohesion between the polymer and the HA. Thehot mixture was stirred together and fed to an injection mouldingmachine. Moulded components were produced which had HA particlesembedded within their surface.

EXAMPLE 5

[0034] A calcium carbonate (CC) powder having a maximum particle size ofabout 50 microns was put into a pan granulator. While tumbling, the CCpowder was sprayed with a solution of poly L-lactide of molecular weight150,000 Daltons in chloroform at a concentration of 2 gms PLLA in 100 mlof chloroform. Spraying was stopped when the granules reached a maximumsize of approximately 3 mm. The product was dried at 100° C. for 2 hoursto remove residual solvent and any remaining powder less than 500 micronparticle size was sieved out of the mix. The granulated CC was now dryblended with PLLA granules of molecular weight 220,000 Daltons andparticle size 2 mm to 3 mm in a weight ratio of PLLA:CC, 2:1. Themixture was fed to an injection moulding machine and moulded componentswere produced which had CC particles embedded within their surface.

EXAMPLE 6

[0035] A material was prepared according to any of the methods describedin Examples 1 through 5. However the bioabsorbable polymer component wasa poly L-lactide having a molecular weight of 450,000 Daltons.

EXAMPLE 7

[0036] A material was prepared according to any of the methods describedin the preceding examples. In each case the filler component included aproportion of sodium chloride ranging between 1% and 99% of the totalweight of the filler.

[0037] SEM micrographs of the surfaces of components produced by theabove methods show filler particles embedded within the surface of thecomponents, and uniformly distributed therein. The accompanying drawingshows such a micrograph with calcium phosphate filler particles shown inthe surface by the letter X.

[0038] There is thus described a biologically acceptable material andinjection or compression moulded components made from this material,along with a method of making the material and the components. Thecomponents can be used as prosthesis devices which have mechanicalproperties much closer to natural bone than those for instance of metalsor polymers. The materials are at least partially bioabsorbable as aresult of the nature of the materials. Such components do not thereforerequire to be removed from the body following natural healing.

[0039] Polyester polymers degrade through hydrolysis of the ester bondin the polymer backbone to produce simple acid repeat units which can besafely metabolised by the body. The degradation rate depends upon thehydrophilic/hydrophobic nature of the polymer along with the molecularweight (Mw), and degree of crystallinity. The rate of degradation ischosen to allow the healing bone to gradually restore its physiologicalload-bearing function.

[0040] It is to be realised that materials having differing rates ofresorption can be obtained by selection of different polymers orcombinations of polymers, or different Mw, or proportions of fillermaterial. The presence of filler particles moulded within the surface ofthe components provides a surface which is less hydrophobic and moreamenable to early cellular attachment and proliferation than a simplepolymer surface. The inclusion of particles of a sacrificial porosifierenables the production of component implant devices that contain lesspolymer and that have a controlled porosity pre or post implantation.

[0041] The powder feed to the moulding machine contains no mechanicallyfree filler particles substantially less than 100 microns diameter, asthe particles are either loosely bound together, and/or are looselybound with the polymer. The moulded component though contains no fillerparticles substantially greater than 100 microns diameter. Coarserparticles in the moulded component could result in flaws or centres ofweakness.

[0042] The addition of fillers can provide a number of advantages suchas resulting in increasing modulus such that matching of the modulus tobone can be achieved or at least approached. Hydroxyapatite or betatri-calcium phosphate are osteoconductive which helps to provide anenvironment for new bone in-growth as the polymer resorbs. These fillermaterials have a radio density similar to bone and therefore help toenable the implant to be imaged using standard X-ray techniques. Thefillers can also help to prevent the lowering of pH which can occurduring degradation of the polymers due to the acid products beingreleased, which may not be able to diffuse sufficiently quickly away.The powder feed to the moulding machine contains filler particles whichare not fully encapsulated by the polymer and have not been compoundedby a melting process. Such melting would tend to prevent fillerparticles being provided on the surface of the components.

[0043] Various other modifications may be made without departing fromthe scope of the invention. For instance, different materials may beusable. Instead of the fillers indicated in the examples, otherbioactive materials could be used such as calcium carbonate, calciumsulphate or bioactive glass. The filler may comprise a sacrificialporosifier other than sodium chloride which may additionally compriseand constitute a therapeutic agent for controlled release. Theconditions during formation of the material and the components can beadjusted as is required. The components may be annealed to removestresses following formation. Moulding techniques other than injectionmoulding may be used, such as compression moulding, melt spinning orextrusion. The components may be drawn in order to align the polymerchains following formation. Alternative solvents to chloroform may beused.

[0044] Whilst endeavouring in the foregoing specification to drawattention to those features of the invention believed to be ofparticular importance it should be understood that the Applicant claimsprotection in respect of any patentable feature or combination offeatures hereinbefore referred to and/or shown in the drawings whetheror not particular emphasis has been placed thereon.

1. A component made of a biodegradable material which material comprisesa bioabsorbable polymer component and a bioactive filler materialcharacterised in that particles of the filler occur embedded within thesurface of the component.
 2. A component according to claim 1characterised in that, the component comprises any of a screw, pin,plate, suture, wound care patch, spinal spacer, osteotomy wedge, cementrestrictor, non-woven mesh or other item usable in surgery and relatedfields of medicine.
 3. A method of making a biodegradable materialusable to make a component according to claim 1, characterised in thatthe method comprises mixing together a bioabsorbable polymer componentand a bioactive filler material.
 4. A method according to claim 3characterised in that, the polymer component and filler are mixedtogether in the form of granules each having similar particle sizeranges.
 5. A method according to claim 3 characterised in that, theparticle size is between 0.5 mm and 5 mm.
 6. A method according to claim3 characterised in that, the polymer component and filler are mixedtogether in the form of dry particulate materials.
 7. A method accordingto claim 3 characterised in that, the polymer component is coated withthe filler.
 8. A method according to claim 3 characterised in that, thepolymer component is wetted with a solvent prior to or during mixing. 9.A method according to claim 8 characterised in that, the solventcomprises chloroform.
 10. A method according to claim 8 characterised inthat, the polymer component is sprayed onto the filler.
 11. A methodaccording to the claim 8 characterised in that, the material issubsequently dried to remove the solvent.
 12. A method according toclaim 3 characterised in that, the particle size of the polymercomponent is reduced prior to mixing with the filler.
 13. A methodaccording to claim 12 characterised in that, the polymer component ismilled.
 14. A method according to claim 13 characterised in that, thepolymer component is cryogenically milled.
 15. A method according toclaim 3 characterised in that, the particle size of the filler isincreased prior to mixing with the polymer component.
 16. A methodaccording to claim 15 characterised in that, the filler material iscaused to agglomerate or granulate.
 17. A biodegradable material,characterised in that, the material is formed by a method according toclaim
 3. 18. A material according to claim 17 characterised in that, themixture is substantially homogenous.
 19. A material according to claim17 characterised in that, the polymer component is synthetic.
 20. Amaterial according to claim 17 characterised in that, the polymercomponent comprises a polyester.
 21. A material according to claim 17characterised in that, the polymer component comprises one or morepolymers or co-polymers of lactic acid (L and/or D), glycolic acid,hydroxybutyric acid, hydroxyvaleric acid, poly dioxanone, polycaprolactone, poly ethylene oxide or poly butylene terephthalate.
 22. Amaterial according to claim 17 characterised in that, the fillercomprises alone or in combination, a calcium phosphate, calcium sulphateor carbonate bioceramic filler, or a bioactive glass.
 23. A materialaccording to claim 22 characterised in that, the filler compriseshydroxyapatite and/or beta tri-calcium phosphate.
 24. A materialaccording to claim 17 characterised in that, the filler has a particlesize of substantially less than 100 microns.
 25. A material according toclaim 17 characterised in that the filler constitutes between 1% and 50%of the mixture by weight.
 26. A material according to claim 25characterised in that, the filler constitutes between 15% and 35% of themixture by weight.
 27. A material according to claim 17 characterised inthat, the filler additionally comprises, alone or in combination, asacrificial porosifier.
 28. A material according to claim 27characterised in that, the sacrificial porosifier comprises a watersoluble, heat stable inorganic salt.
 29. A material according to claim28 characterised in that, the inorganic salt comprises sodium chloride.30. A material according to claim 29 characterised in that, the sodiumchloride is in the form of a finely divided powder.
 31. A materialaccording to claim 29 characterised in that, the sodium chlorideconstitutes between 1% and 50% by weight of the material.
 32. A materialaccording to claim 17 characterised in that, the material substantiallycomprises no mechanically free filler particles with a diameter lessthan 100 microns.
 33. A method of making a component according to claim1, characterised in that, the method comprises moulding a materialaccording to claim
 17. 34. A method according to claim 33 characterisedin that, the moulding is in the form of a selected one of injectionmoulding, compression moulding, extrusion, extrusion followed by aselected melt forming technique.
 35. A method according to claim 33characterised in that, the material is fed to a moulding machine, withat least a substantial proportion of the material in the form ofgranules with a diameter of between 0.5 and 5 mm.
 36. A method accordingto claim 33 characterised in that, the material is dried prior tomoulding.
 37. A method according to claim 33 characterised in that, thecomponent is annealed subsequent to moulding.